Glycocalyx, the characteristic first line of interaction between membrane and environment, can be visualized as a polyelectrolyte anchored to a bending-resistant matrix. This structure has an amazing resemblance with the ionized monolayers, in which, the cohesion among hydrocarbon chains is counteracted by the repulsion among similarly charged ionic heads, and thus the balance determines the curvature of the membrane. Likewise, it could be assumed that in biological membranes, repulsion among similarly charged groups in the glycocalyx could generate different curving trends. Hence, the factors directly influencing the electrostatic interaction among surface charged groups were studied, assessing the effect of the medium's ionic strength (mu) and pH, in an extensive range of values around the physiological one. The results point out mu variations inducing different shapes, depending on whether mu values were lower or higher than the physiological ones; which could be explained by the polyelectrolyte theory. The occurrence of more invaginated shapes as the medium's pH decreases, and the opposite event, when the pH increases, could be attributed to the coupling between the dissociation of the glycocalyx ionic groups and the H+ concentration. The behavior of the cells with reduced surface charges (by neuraminidase degradation) supports the hypothesis that the observed mu and the pH effect on erythrocyte shape could be mediated by glycocalyx charged groups.